On October 7, 2023, about 4,000 civilians attending the Nova open-air music festival in southern Israel were the victims of a sudden terrorist attack. They had to swiftly react to the attack by running and hiding for extended periods of time to protect their lives.

At the time of the attack, a significant proportion of these people were under the influence of various recreational drugs. We hypothesized that the pre-trauma use of psychostimulants or hallucinogens would be significantly associated with the severity of peri-traumatic dissociation, anxiety, depression, and acute stress disorder (ASD) symptoms in survivors of the attack.

Two hundred thirty-two survivors sought assistance at the Chaim Sheba Medical Center and underwent clinical evaluation. They were considered for this study if they had no severe physical injuries; no first-degree family member killed during the attack; and no history of mental disorders, including post-traumatic stress disorder (PTSD).

Of the 232 survivors screened for the study, 126 met the above criteria and provided informed consent to participate. However, two of them who reported using hallucinogenic mushrooms, and one who reported using ketamine prior to the traumatic event, were excluded from the analysis, due to the small sample size for these drugs, leaving a sample of 123 participants. Their mean age (±SE) was 28.4±0.7 years; 75 of them (60.9%) were male; 68.9% were never married, and 68.2% were holding a high-school degree or equivalent.

Seventy-one of them (57.7%) reported using psychoactive drugs at the festival – 12 only alcohol, nine only lysergic acid (LSD), seven only 3,4-methylenedioxymethamphetamine (MDMA), six only cannabis, three only methylmethcathinone (MMC), 15 various drug combinations including alcohol, and 19 various drug combinations excluding alcohol.

All participants completed several questionnaires, assessing peri-traumatic dissociation (Peritraumatic Dissociative Experiences Questionnaire, PDEQ), post-traumatic anxiety (Generalized Anxiety Disorder-7, GAD-7; and Visual Analog Scale for Anxiety, VAS-A), depression (Patient Health Questionnaire-9, PHQ-9), and ASD symptoms (Posttraumatic Diagnostic Scale, PDS-5).

Both the GAD-7 scores and the PDS-5 hyperarousal scores were significantly higher in the drug-user than in the drug-free group (p<0.05 and p<0.008, respectively). The scores of most participants were above the clinical threshold for these instruments (>10 for GAD-7 in 70.4%, and >28 for PDS-5 in 81.3% of the participants), indicating a very high level of anxiety- and hyperarousal-related symptoms in both groups. Both the PDEQ and PHQ-9 scores were higher in the drug-user than in the drug-free group, but the differences were not significant. No significant differences were found between the groups in the VAS-A, total PDS-5, and PDS-5 subscales. The VAS-A scores of 51.9% of the participants were higher than 6, which is the clinical threshold for this instrument.

A multiple regression analysis was performed on the scores of the PDEQ, PHQ-9, GAD-7, PDS-5 (total and subscales), and VAS-A questionnaires, employing nine sets of independent variables related to drug use, gender and age (see supplementary information).

The multiple regression model for the PDEQ scores was statistically significant (p=0.018). The severity of peri-traumatic dissociation was significantly correlated with alcohol consumption prior to the event (β=0.25, p<0.008), but not with the consumption of any other drug. Consuming alcohol prior to the traumatic event, as compared with consuming other drugs, significantly increased the likelihood of experiencing peri-traumatic dissociation (PDEQ score = 24.8±2.0 vs. 19.3±1.0, p<0.015).

The model for the PHQ-9 scores was statistically significant (p=0.02). The severity of depressive symptoms was significantly correlated with alcohol consumption prior to the event (β=0.32, p<0.001), but not with the consumption of any other drug. Consuming alcohol prior to the event, as compared with consuming other drugs, significantly increased the likelihood of depressive symptoms (PHQ-9 score = 18.7±1.8 vs. 13.8±0.6, p<0.0015).

The model for the GAD-7 scores was statistically significant (p=0.04). The severity of anxiety symptoms was significantly correlated with alcohol consumption prior to the event (β=0.29, p<0.002). Consuming alcohol, as compared with consuming other drugs prior to the event, significantly increased the likelihood of anxiety (GAD-7 score = 16.3±1.0 vs. 12.7±0.6, p<0.004). None of the other drugs consumed prior to the event significantly affected symptoms of anxiety.

The model for the PDS-5 arousal-hyperactivity scores was statistically significant (p=0.03). The severity of arousal and hyperactivity symptoms was significantly correlated with alcohol (β=0.24, p<0.011) and MMC (β=0.24, p<0.011) consumption prior to the traumatic event. Both alcohol and MMC consumption significantly increased the likelihood of experiencing arousal and hyperactivity symptoms, as compared with the consumption of other drugs.

The multiple regression analysis of the PDEQ dissociation score with VAS-A, GAD-7, PHQ-9, and PDS-5 subscale scores, including gender and age, was statistically significant (p=0.0001). Experiencing peri-traumatic dissociation was significantly correlated with the VAS-A score (β=0.31, p<0.02) and with the PDS-5 mood score (β=0.28, p<0.045).

A mediation analysis showed that pre-trauma alcohol consumption positively predicted PDS-5 mood scores (β=0.15, p=0.03), PDS-5 arousal scores (β=0.16, p=0.015), PDS-5 intrusive scores (β=0.23, p=0.001), GAD-7 anxiety scores (β=0.20, p=0.0015), PHQ-9 depression scores (β=0.24, p=0.00025), and PDEQ peri-traumatic dissociation scores (β=0.20, p=0.01). With the introduction of the peri-traumatic dissociation variable into the model as a potential mediator, the association between alcohol consumption and PDS-5 mood, PDS-5 intrusive, GAD-7 anxiety and PHQ-9 depressive scores became less significant (p<0.04, p<0.015, p<0.015 and p<0.02, respectively). This finding suggests that peri-traumatic dissociation partially mediated the association between alcohol consumption and mood, intrusion, anxiety and depressive symptoms.

So, in marked contrast to our expectations, we found that only pre-trauma alcohol consumption, with or without other drugs, significantly increased the risk of peri-traumatic dissociation, anxiety, depression, and ASD symptoms.

Alcohol consumption exerts various effects on brain functions and behavior, ranging from anxiolytic and mild disinhibitory effects to sedation, motor incoordination, altered memory and emotional processing^{1, 2}. Therefore, pre-trauma alcohol consumption may have interfered with the cognitive, emotional and physiological processes necessary to cope with the traumatic event. The previously available evidence on the effect of pre-trauma alcohol use on the development of post-traumatic symptomatology was mixed^3-7.

Importantly, the traumatic event was prolonged (participants had to run and hide for 8-20 hours until they were rescued). Therefore, the survivors may have experienced a hangover, which could have increased their anxiety and traumatic stress⁸.

We also found that peri-traumatic dissociation significantly increased the likelihood of subsequent anxiety and mood symptoms in participants who consumed alcohol. Peri-traumatic dissociation can potentially disrupt the processing and integration of traumatic memories, which may impede recovery and increase the probability of developing post-traumatic disorders, because trauma-related memories persist in a fragmented and unprocessed state⁹.

The Nova massacre provides a unique opportunity to study how pre-trauma drug consumption affects post-trauma mental health outcomes. Yet, our study is not devoid of limitations. First, as in all naturalistic studies, the sample size is constrained. Second, we relied only on the reports of the participants on their consumption of drugs, rather than on measurements of blood concentrations and data regarding the actual quantities of the consumed substances, which hampers a more nuanced understanding of the correlation between drug consumption and the observed outcomes.

Nonetheless, this study presents novel insights into the relationship between pre-trauma alcohol consumption and increased vulnerability to peri-traumatic dissociation, anxiety, depression, and ASD symptoms. Given the widespread prevalence of alcohol consumption in social gatherings – and the increasing occurrence of sexual assaults, physical assaults and vehicular accidents – these findings can have a social and clinical interest. Moreover, since alcohol is a compound with a known pharmacology and mode of action, they can be relevant to the elucidation of the biology of response to traumatic experiences.

2023年10月7日，以色列南部参加诺瓦露天音乐节的约4000名平民遭遇突如其来的恐怖袭击。他们必须对袭击做出迅速反应，长时间奔跑和躲藏以保护自己的生命。

袭击发生时，这些人中有很大一部分人受到各种娱乐性药物的影响。我们假设，创伤前使用精神兴奋剂或致幻剂与袭击幸存者的创伤周围分离、焦虑、抑郁和急性应激障碍 (ASD) 症状的严重程度显着相关。

232 名幸存者在 Chaim Sheba 医疗中心寻求帮助并接受了临床评估。如果他们没有严重的身体伤害，他们就会被考虑参加这项研究；没有一级家庭成员在袭击中丧生；无精神疾病史，包括创伤后应激障碍 (PTSD)。

在本研究筛选的 232 名幸存者中，有 126 名符合上述标准并知情同意参与。然而，其中两名报告使用致幻蘑菇的人，以及一名报告在创伤事件前使用氯胺酮的人，由于这些药物的样本量较小，被排除在分析之外，留下 123 名参与者的样本。他们的平均年龄 (±SE) 为 28.4±0.7 岁；其中男性 75 人（60.9%）； 68.9%的人从未结过婚，68.2%的人拥有高中或同等学历。

其中 71 人 (57.7%) 报告在节日期间使用了精神活性药物，其中 12 人仅使用酒精，9 人仅使用麦角酸 (LSD)，7 人仅使用 3,4-亚甲二氧基甲基苯丙胺 (MDMA)，6 人仅使用大麻，3 人仅使用甲基卡西酮 (MMC) ，15种含酒精的各种药物组合，以及19种不含酒精的各种药物组合。

所有参与者都完成了几份问卷，评估创伤周围解离（创伤周围解离体验问卷，PDEQ）、创伤后焦虑（广泛性焦虑症-7，GAD-7；和焦虑视觉模拟量表，VAS-A）、抑郁（患者健康问卷-9，PHQ-9）和自闭症谱系障碍症状（创伤后诊断量表，PDS-5）。

吸毒者的 GAD-7 评分和 PDS-5 过度警觉评分均显着高于未吸毒组（分别为 p<0.05 和 p<0.008）。大多数参与者的分数高于这些仪器的临床阈值（70.4% 的参与者中 GAD-7 为 >10，81.3% 的参与者中 PDS-5 为 >28），表明焦虑和过度警觉水平非常高两组的相关症状。吸毒者的PDEQ和PHQ-9评分均高于未吸毒者，但差异不显着。各组之间的 VAS-A、总 PDS-5 和 PDS-5 分量表未发现显着差异。 51.9%的参与者的VAS-A评分高于6分，这是该仪器的临床阈值。

使用与药物使用、性别和年龄相关的九组自变量，对 PDEQ、PHQ-9、GAD-7、PDS-5（总量表和子量表）和 VAS-A 问卷的分数进行多元回归分析（参见补充信息）。

PDEQ 分数的多元回归模型具有统计显着性 (p=0.018)。创伤周围解离的严重程度与事件前的饮酒量显着相关（β=0.25，p<0.008），但与任何其他药物的消耗量无关。与服用其他药物相比，在创伤事件之前饮酒会显着增加经历创伤周围解离的可能性（PDEQ 评分 = 24.8±2.0 与 19.3±1.0，p<0.015）。

PHQ-9 评分模型具有统计显着性 (p=0.02)。抑郁症状的严重程度与事件发生前的饮酒量显着相关（β=0.32，p<0.001），但与任何其他药物的消耗量无关。与服用其他药物相比，在事件发生前饮酒会显着增加抑郁症状的可能性（PHQ-9 评分 = 18.7±1.8 与 13.8±0.6，p<0.0015）。

GAD-7 评分模型具有统计显着性 (p=0.04)。焦虑症状的严重程度与事件发生前的饮酒量显着相关（β=0.29，p<0.002）。与事件发生前服用其他药物相比，饮酒显着增加了焦虑的可能性（GAD-7 评分 = 16.3±1.0 与 12.7±0.6，p<0.004）。事件发生前服用的其他药物均未显着影响焦虑症状。

PDS-5 唤醒多动评分模型具有统计显着性 (p=0.03)。觉醒和多动症状的严重程度与创伤事件前的酒精（β=0.24，p<0.011）和MMC（β=0.24，p<0.011）消耗量显着相关。与服用其他药物相比，饮酒和 MMC 的服用都会显着增加出现兴奋和多动症状的可能性。

PDEQ 解离评分与 VAS-A、GAD-7、PHQ-9 和 PDS-5 子量表评分（包括性别和年龄）的多元回归分析具有统计学显着性（p=0.0001）。经历创伤周围分离与 VAS-A 评分（β=0.31，p<0.02）和 PDS-5 情绪评分（β=0.28，p<0.045）显着相关。

中介分析表明，创伤前饮酒可正向预测 PDS-5 情绪评分（β=0.15，p=0.03）、PDS-5 唤醒评分（β=0.16，p=0.015）、PDS-5 侵入评分（β= 0.23，p=0.001）、GAD-7 焦虑评分（β=0.20，p=0.0015）、PHQ-9 抑郁评分（β=0.24，p=0.00025）和 PDEQ 创伤周围解离评分（β=0.20，p） =0.01）。随着将创伤周围解离变量作为潜在中介引入模型中，饮酒与 PDS-5 情绪、PDS-5 侵入性、GAD-7 焦虑和 PHQ-9 抑郁评分之间的关​​联变得不那么显着（p%分别为 3C0.04、p<0.015、p<0.015 和 p<0.02）。这一发现表明，创伤周围的分离部分介导了饮酒与情绪、入侵、焦虑和抑郁症状之间的关联。

因此，与我们的预期形成鲜明对比的是，我们发现，只有创伤前饮酒，无论是否服用其他药物，都会显着增加创伤周围分离、焦虑、抑郁和自闭症谱系障碍症状的风险。

饮酒对大脑功能和行为产生多种影响，从抗焦虑和轻度去抑制作用到镇静、运动不协调、记忆和情绪处理改变^{1, 2} 。因此，创伤前饮酒可能会干扰应对创伤事件所需的认知、情感和生理过程。先前关于创伤前饮酒对创伤后症状发展的影响的证据是混杂的^3-7 。

重要的是，创伤事件持续了很长时间（参与者必须逃跑并躲藏8-20小时，直到获救）。因此，幸存者可能经历了宿醉，这可能会增加他们的焦虑和创伤压力⁸ 。

我们还发现，饮酒的参与者在创伤前后的分离显着增加了随后出现焦虑和情绪症状的可能性。创伤周围的分离可能会破坏创伤记忆的处理和整合，这可能会阻碍康复并增加发生创伤后疾病的可能性，因为与创伤相关的记忆持续处于支离破碎和未经处理的状态⁹ 。

新星大屠杀提供了一个独特的机会来研究创伤前药物消费如何影响创伤后心理健康结果。然而，我们的研究并非没有局限性。首先，与所有自然主义研究一样，样本量受到限制。其次，我们仅依赖于参与者关于药物消耗的报告，而不是血液浓度的测量和有关消耗物质的实际数量的数据，这妨碍了对药物消耗与观察到的药物之间的相关性的更细致的了解。结果。

尽管如此，这项研究对创伤前饮酒与创伤周围分离、焦虑、抑郁和自闭症谱系障碍症状的脆弱性增加之间的关系提出了新的见解。鉴于社交聚会中饮酒的普遍现象，以及性侵犯、人身攻击和车辆事故的不断增加，这些发现可能会引起社会和临床的兴趣。此外，由于酒精是一种具有已知药理学和作用方式的化合物，因此它们可能与阐明创伤经历反应的生物学相关。